Benzylpenicillin sodium Intravenous Infusion: It is recommended that 600 mg (1 mega

unit) should be dissolved in at least 10 ml of Sodium Chloride

600mg and 1200mg
Powder for Injection
Technical Leaflet
PRODUCT SUMMARY
Qualitative and Quantitative Composition
Benzylpenicillin sodium available as 600 mg and 1200 mg vials.
Pharmaceutical Form
White crystalline, water-soluble sterile powder for injection.
CLINICAL PARTICULARS
Therapeutic indications:
Benzylpenicillin is indicated for most wound infections, pyogenic
infections of the skin, soft tissue infections and infections of the
nose, throat, nasal sinuses, respiratory tract and middle ear, etc.
It is also indicated for the following infections caused by
penicillin-sensitive microorganisms: Generalised infections,
septicaemia and pyaemia from susceptible bacteria. Acute and
chronic osteomyelitis, sub-acute bacterial endocarditis and
meningitis caused by susceptible organisms. Suspected
meningococcal disease. Gas gangrene, tetanus, actinomycosis,
anthrax, leptospirosis, rat-bite fever, listeriosis, severe Lyme
disease, and prevention of neonatal group B streptococcal
infections. Complications secondary to gonorrhoea and syphilis
(e.g. gonococcal arthritis or endocarditis, congenital syphilis and
neurosyphilis). Diphtheria, brain abscesses and pasteurellosis.
Consideration should be given to official local guidance
(e.g. national recommendations) on the appropriate use of
antibacterial agents.
Susceptibility of the causative organism to the treatment should
be tested (if possible), although therapy may be initiated before
the results are available.
Posology and method of administration
Route of administration:
Intramuscular, intravenous.
Preparation of solutions:
Pharmaceutical preparation
Only freshly prepared solutions should be used. Reconstituted
solutions of benzylpenicillin sodium are intended for
immediate administration.
600 mg vial
Intramuscular injection: 600 mg (1 mega unit) is usually
dissolved in 1.6 to 2 ml of Water for Injections BP.
600 mg and 1200 mg vials
Intravenous Injection: A suitable concentration is 600 mg
(1 mega unit) dissolved in 4 to 10 ml of Water for Injections BP
or Sodium Chloride Injection BP and 1200 mg (2 mega units)
dissolved in at least 8 ml of Sodium Chloride Injection BP or Water
for Injections BP.
Injection BP or Water for Injections BP and 1200 mg (2 mega
units) should be dissolved in at least 20 ml of Sodium Chloride
Injection BP or Water for Injections BP. Sodium overload and/or
heart failure may occur if benzylpenicillin sodium is
administered in sodium-containing solvents to patients who
suffer from renal failure and/or heart failure. Therefore, for such
patients, benzylpenicillin sodium should not be reconstituted in
sodium-containing liquids such as Sodium Chloride Injection BP or
Ringer’s solution.
Dosage and administration:
The following dosages apply to both intramuscular and
intravenous injection.
Alternate sites should be used for repeated injections.
Adults
600 to 3,600 mg (1 to 6 mega units) daily, divided into 4 to 6
doses, depending on the indication. Higher doses (up to 14.4
g/day (24 mega units) in divided doses) may be given in serious
infections such as adult meningitis by the intravenous route.
In bacterial endocarditis, 7.2 to 12 g (12 to 20 mega units) or
more may be given daily in divided doses by the intravenous
route, often by infusion.
Doses up to 43.2 g (72 mega units) per day may be necessary
for patients with rapidly spreading gas gangrene.
High doses should be administered by intravenous injection or
infusion, with intravenous doses in excess of 1.2g (2 mega units)
being given slowly, taking at least one minute for each 300 mg
(0.5 mega unit) to avoid high levels causing irritation of the
central nervous system and/or electrolyte imbalance.
High dosage of benzylpenicillin sodium may result in
hypernatraemia and hypokalaemia unless the sodium content
is taken into account.
For the prevention of Group B Streptococcal disease of the
newborn, a 3 g (5 mega units) loading dose should be given to the
mother initially, followed by 1.5 g (2.5 mega units) every 4 hours
until delivery.
Children aged 1 month to 12 years
100 mg/kg/day in 4 divided doses; not exceeding 4 g/day.
Infants 1-4 weeks
75 mg/kg/day in 3 divided doses.
Newborn Infants
50 mg/kg/day in 2 divided doses.
Meningococcal disease
Children 1 month to 12 years:
180-300 mg/kg/day in 4-6 divided doses,
not exceeding 12 g/day.
Infants 1-4 weeks: 150 mg/kg/day in 3 divided doses.
Newborn infants: 100 mg/kg/day in 2 divided doses.
Adults and children over 12 years:
2.4 g every 4 hours
Suspected meningococcal disease
If meningococcal disease is suspected general practitioners
may be helpful. In patients undergoing high-dose treatment for
more than 5 days, electrolyte balance, blood counts and renal
should give a single dose of benzylpenicillin sodium, before
transferring the patient to hospital, as follows:
functions should be monitored.
In the presence of impaired renal function, large doses of
Adults and children over 10 years: 1,200 mg IV (or IM) penicillin can cause cerebral irritation, convulsions and coma.
Children 1-9 years: 600 mg IV (or IM)
Children under 1 year: 300 mg IV (or IM)
Skin sensitisation may occur in persons handling the antibiotic
and care should be taken to avoid contact with the substance.
Premature babies and neonates
It should be recognised that any patient with a history of allergy,
Dosing should not be more frequent than every 8 or 12 hours in especially to drugs, is more likely to develop a hypersensitivity
this age group, since renal clearance is reduced at this age and reaction to penicillin. Patients should be observed for 30 minutes
the mean half-life of benzylpenicillin may be as long as 3 hours. after administration and if an allergic reaction occurs the drug
Since infants have been found to develop severe local reactions
should be withdrawn and appropriate treatment given.
to intramuscular injections, intravenous treatment should
Delayed absorption from the intramuscular depot may occur in
preferably be used.
diabetics.
Patients with renal insufficiency
Prolonged use of benzylpenicillin may occasionally result in an
For doses of 0.6-1.2 g (1-2 mega units) the dosing interval should
overgrowth of non-susceptible organisms or yeast and patients
be no more frequent than every 8-10 hours.
should be observed carefully for superinfections.
For high doses e.g. 14.4 g (24 mega units) required for the
treatment of serious infections such as meningitis, the dosage Pseudomembranous colitis should be considered in patients who
and dose interval of benzylpenicillin sodium should be develop severe and persistent diarrhoea during or after receiving
adjusted in accordance with the following schedule: benzylpenicillin. In this situation, even if Clostridium difficile is
only suspected, administration of benzylpenicillin should be
Creatine clearance Dose Dose Dosing interval discontinued and appropriate treatment given.
(ml per minute) (g) (mega units) (hours)
1.2 2 2 Interaction with other medicaments and other forms
125 or or of medication
1.8 3 3
The efficacy of oral contraceptives may be impaired under
60 1.2 2 4 concomitant administration of benzylpenicillin sodium, which
may result in unwanted pregnancy. Women taking oral
40 0.9 1.5 4 contraceptives should be aware of this and should be informed
about alternative methods of contraception.
20 0.6 1.0 4
There is reduced excretion of methotrexate (and therefore
increased risk of methotrexate toxicity) when used with
10 0.6 1.0 6
benzylpenicillin sodium.
0.3 0.5 6 Probenecid inhibits tubular secretion of benzylpenicillin sodium
Nil or or
and so may be given to increase the plasma concentrations.
0.6 1.0 8
Penicillins may interfere with:
The dose in the above table should be further reduced to 300 mg • Urinary glucose tests
(0.5 mega units) 8 hourly if advanced liver disease is associated • Coombs’ tests
• Tests for urinary or serum proteins
with severe renal failure.
• Tests which use bacteria e.g. Guthrie test
If haemodialysis is required, an additional dose of 300 mg
(0.5 mega units) should be given 6 hourly during the procedure. Pregnancy and lactation
Benzylpenicillin sodium has been taken by a large number
Elderly Patients
of pregnant women and women of childbearing age without an
Elimination may be delayed in elderly patients and dose reduction increase in malformations or other direct or indirect harmful
may be necessary. effects on the foetus having been observed.
Contraindications Although it is not known if benzylpenicillin sodium may be
Allergy to penicillins. Hypersensitivity to any ingredient of the
excreted into the breast milk of nursing mothers, it is actively
preparation.
transported from the blood to milk in animals and trace amounts
Cross allergy to other beta-lactams such as cephalosporins should of other penicillins in human milk have been detected.
be taken into account.
Special warnings, special precautions
600 mg benzylpenicillin contains 1.68 mmol of sodium. Massive
doses of benzylpenicillin sodium can cause hypokalaemia and
sometimes hypernatraemia. Use of a potassium-sparing diuretic

PACKAGE LEAFLET: INFORMATION FOR THE USER 1. WHAT BENZYLPENICILLIN INJECTION IS AND WHAT IT IS Benzylpenicillin sodium is also used for the prevention of infection Probenecid may make the effects of Benzylpenicillin last for longer.

Benzylpenicillin sodium USED FOR

Benzylpenicillin sodium 600mg and 1200mg Powder for Injection
in newborn babies (specifically group B streptococcal infection). Benzylpenicillin can make it more likely to get side-effects from
methotrexate and can sometimes make oral contraceptives less
600mg and 1200mg is referred to as “Benzylpenicillin Injection” in this leaflet. It
contains benzylpenicillin sodium, also known as penicillin G.
2. BEFORE YOU USE BENZYLPENICILLIN INJECTION
Do not use Benzylpenicillin Injection if you:
effective, resulting in unplanned pregnancy.
Penicillins can interfere with the results of certain urine and blood
Powder for Injection Benzylpenicillin sodium is one of a group of medicines known as
penicillins, which are antibiotics. Antibiotics are used to kill the
• are allergic (hypersensitive) to benzylpenicillin sodium, any
other antibiotics (in particular other penicillins,
tests.
Pregnancy and breast-feeding
bacteria (germs) which cause infections. cephalosporins or beta-lactams) or any of the other ingredients Ask your doctor or pharmacist for advice before taking any
Read all of this leaflet carefully before you start taking this Benzylpenicillin sodium is used to treat infections of the: (see section 6 - Further information). medicine.
medicine. • ear • heart Take special care with Benzylpenicillin Injection if you:
- Keep this leaflet. You may need to read it again. • nose • bones • suffer from other allergies, especially an allergy to medicines 3. HOW TO USE BENZYLPENICILLIN INJECTION
- If you have any further questions, ask your doctor or • throat • skin. • are pregnant, breast-feeding or think you could be pregnant Your doctor will mix the benzylpenicillin sodium powder with an
pharmacist. • chest • have kidney problems injection solution, which is usually water for injections or sodium
- This medicine has been prescribed for you. Do not pass it • have liver problems chloride, before injecting it. (Sodium chloride injection will not be
on to others. It may harm them, even if their symptoms are It may also be used to treat: • have any heart problems used if you have kidney or heart problems.)
the same as yours. • some sexually transmitted • listeria (a type of food • are diabetic. Your medicine will be injected either intramuscularly (into the
- If any of the side-effects get serious, or if you notice any infections (gonorrhoea and poisoning) muscle) or intravenously (into a vein). Repeated injections will be
syphilis) • leptospirosis (an infection Using other medicines
side-effects not listed in this leaflet, please tell your doctor or given at different sites. Infants and diabetics will normally receive
• meningitis from animals) Please tell your doctor or pharmacist if you are taking or have
pharmacist. Benzylpenicillin into a vein.
• brain abscesses • pasteurellosis (an infection recently taken any other medicines, including medicines obtained
• gangrene (decay and death following animal bites) without a prescription.
In this leaflet:
of tissue due to lack of • severe Lyme disease (an Take care if you are taking any of the following medicines:
1. What Benzylpenicillin Injection is and what it is used for
blood supply) infection from tick bites) • oral contraceptives
2. Before you use Benzylpenicillin Injection
• blood infections • actinomycosis (an infection • probenecid for the treatment of gout (inflammation of the
3. How to use Benzylpenicillin Injection
• anthrax (an infection from caused by trauma/surgery) joints, especially the big toe) Please read the back of this leaflet.
4. Possible side-effects
animals) • some infections caused by • methotrexate for the treatment of certain cancers
5. How to store Benzylpenicillin Injection
• tetanus rat bites. • allopurinol or sulfinpyrazone - treatments for gout
6. Further information
• diphtheria (acute • neomycin - an antibiotic
infections/disease of the • anti-coagulants - medicines that prevent blood clots
respiratory tract) • oral typhoid vaccine. 92797761805

*Trademark

GEN/BZP/PIL/336_05
14/09/2016
Technical Leaflet (continued) Breakpoints: Insusceptible micro-organisms PHARMACEUTICAL PARTICULARS
The tentative breakpoints (British Society for Antimicrobial Type of Micro-organism Micro-organism Range of acquired
resistance
List of excipients
Effects on ability to drive and use machines Chemotherapy, BSAC) for benzylpenicillin sodium are as None
Aerobic Gram-positive • Coagulase negative Staphylococcus 71-81%*
None follows: micro-organisms Incompatibilities
• Enterococcus Spp Resistant
Undesirable effects Organism S <– (mg/L) I (mg/L) R >– (mg/L) • Staphylococcus aureus 79-87%* benzylpenicillin sodium and solutions that contain metal ions
Blood and Lymphatic System Disorders • Acinetobacter Resistant
should be administered separately.
Streptococcus pneumoniae 0.06 0.12–1.0 2.0 Aerobic Gram-negative
Rare (0.01% - 0.1%) Neisseria gonorrhoeae micro-organisms • Bordetella pertussis Generally resistant Benzylpenicillin sodium should not be administered in the same
Haemolytic anaemia and granulocytopenia (neutropenia), Neisseria meningitides 0.06 0.12 • Brucella spp. Resistant
syringe/giving set as amphotericin B, cimetidine, cytarabine,
agranulocytosis, leucopenia and thrombocytopenia, have • Enterobacteriaceae (including Escherichia flucloxacillin, hydroxyzine, methylprednisolone, or promethazine
Haemolytic streptococci 0.12 0.25
been reported in patients receiving prolonged high doses of Staphylococci
coli, Salmonella, Shigella, Enterobacter, Generally resistant since it is incompatible with these drugs.
Klebsiella, Proteus, Citrobacter).
benzylpenicillin sodium (eg. Subacute bacterial endocarditis). Moraxella catarrhalis
• Haemophilus influenzae Resistant Shelf-life
Haemophilus influenzae
Immune System Disorders • Pseudomonas Resistant Unopened 36 months.
Very Common (>10%)
Rapidly growing anaerobes 1.0 2.0 Anaerobic • Bacteroides fragilis 100%*** Reconstituted product should be used immediately.
micro-organisms
Patients undergoing treatment for syphilis or neurosyphilis with Special precautions for storage
S = Susceptible, I = Intermediate susceptibility, R = Resistant
benzylpenicillin may develop a Jarisch-Herxheimer reaction. * UK data, ** European data, ***Global data Store below 25°C.
Common (1-10%) Susceptibility: Nature and contents of container
Hypersensitivity to penicillin in the form of rashes (all types), Other Information: Tubular type Ill glass vials sealed with bromobutyl rubber plugs with
The prevalence of resistance may vary geographically and with
fever, and serum sickness may occur (1-10% treated patients). time for selected species and local information on resistance is Known Resistance Mechanisms and Cross-resistance aluminium overseals or plastic ‘flip-top’ caps. This product is
These may be treated with antihistamine drugs. desirable, particularly when treating severe infections. supplied in vials containing 600 mg and 1.2 g of powder in boxes
Penicillin resistance can be mediated by alteration of penicillin
Rare (0.01%-0.1%) The following table gives only approximate guidance on binding proteins or development of beta-lactamases. containing 25 vials and “GP pack” containing 2 vials of 600 mg.
More rarely, anaphylactic reactions have been reported probabilities whether micro organisms will be susceptible to Resistance to penicillin may be associated with cross-resistance Instructions for use/handling
(<0.05% treated patients). benzylpenicillin sodium or not. to a variety of other beta lactam antibiotics either due to a shared After contact with skin, wash immediately with water. In case of
Nervous System Disorders target site that is altered, or due to a beta-lactamase with a broad contact with eyes, rinse immediately with plenty of water and
Susceptible and intermediately susceptible micro-organisms
Rare (0.01%-0.1%) range of substrate molecules. In addition to this, cross resistance seek medical advice if discomfort persists.
Type of Micro-organism Micro-organism Range of required
Central nervous system toxicity, including convulsions, has been resistance to unrelated antibiotics can develop due to more than one MARKETING AUTHORISATION HOLDER
reported with massive doses over 60 g per day and in patients Aerobic Gram-positive • Bacillus anthracis 0%** resistance gene being present on a mobile section of DNA Genus Pharmaceuticals,
micro-organisms (e.g. plasmid, transposon etc) resulting in two or more resistance
with severe renal impairment. • Corynebacterium diphtheriae 0%*
Linthwaite, Huddersfield, HD7 5QH, UK.
Renal and Urinary Disorders
• Haemolytic streptococci mechanisms being transferred to a new organism at the same
(including Streptococcus pyogenes) 0%*-3%**
time. MARKETING AUTHORISATION NUMBERS
Rare (0.01%-0.1%) • Listeria monocytogenes 0%**
PL 06831/0213
Interstitial nephritis has been reported after intravenous • Streptococcus pneumoniae 4%*-40%** Pharmacokinetic properties PL 06831/0284
benzylpenicillin sodium at doses of more than 12 g per day. • Streptococcus viridans 3-32%* Benzylpenicillin sodium rapidly appears in the blood following
Reporting of suspected adverse reactions Aerobic Gram-negative • Neisseria gonorrhoeae 9-10%* intramuscular injection of water-soluble salts and maximum DATE OF FIRST AUTHORISATION/ RENEWAL OF
micro-organisms • Neisseria meningitidis 18%* concentrations are usually reached in 15-30 minutes. Peak AUTHORISATION
Reporting suspected adverse reactions after authorisation of the
• Pasteurella multocida 0%*** plasma concentrations of about 12 mcg/ml have been reported 3 July 2008
medicinal product is important. It allows continued monitoring of
the benefit/risk balance of the medicinal product. Healthcare Anaerobic • Actinomyces israelii 8%** after doses of 600 mg with therapeutic plasma concentrations for DATE OF (PARTIAL) REVISION OF THE TEXT
micro-organisms • Fusobacterium nucleatum and
professionals are asked to report any suspected adverse reactions Fusobacterium necrophorum Usually sensitive
most susceptible organisms detectable for about 5 hours. December 2018
via the Yellow Card Scheme at:www.mhra.gov.uk/yellowcard. • Gram-positive sporing bacilli
Approximately 60% of the dose injected is reversibly bound to
(including Clostridium tetani and 14%** plasma protein.
Overdose Clostridium perfringens (welchii))
Excessive blood levels of benzylpenicillin sodium can be • Gram-positive cocci
In adults with normal renal function the plasma half-life is about
corrected by haemodialysis.
(including peptostreptococcus) 7%* 30 minutes. Most of the dose (60-90%) undergoes renal
Other micro-organisms • Borrelia bugdorferi Usually sensitive elimination, 10% by glomerular filtration and 90% by tubular
PHARMACOLOGICAL PROPERTIES • Capnocytophaga canimorosus Usually sensitive secretion. Tubular secretion is inhibited by probenecid, which is
Pharmacodynamic properties • Leptospirae Usually sensitive sometimes given to increase plasma penicillin concentrations.
Pharmacotherapeutic group: Beta-lactamase sensitive penicillins. • Streptobacillus moniliformis and Biliary elimination of benzylpenicillin sodium accounts for only a
spirrillum minus Usually sensitive
ATC code: J01 CE01. minor fraction of the dose.
• Treponema pallidum 0%***
General Properties: Preclinical safety data
benzylpenicillin sodium is a beta-lactam antibiotic. It is * UK data, ** European data, ***Global data There are no pre-clinical data of relevance to the prescriber which
bacteriocidal by inhibiting bacterial cell wall biosynthesis. are additional to that already included in other sections of the
SmPC.

Adults
The usual dose is 600mg to 3,600mg daily.
For severe infections such as meningitis and gangrene, higher
daily doses of up to 14,400mg and 43,200mg respectively may be
used.
Suspected Meningitis:
Benzylpenicillin is sometimes given as a single dose in cases of
suspected meningitis. The usual dose is 1,200mg for adults and
children over 10 years.
Meningitis:
The usual dose is 2,400mg every four hours for adults.
Prevention of infection during labour:
If Benzylpenicillin is administered during labour for the prevention
of infection (specifically group B streptococcal infection) in
newborn babies, 3,000mg of Benzylpenicillin should be given to
the mother followed by 1,500mg every four hours until the baby is
delivered.
Adults with kidney problems
Your doctor will carry out some tests to check this. You may then
be given a lower dose of Benzylpenicillin Injection. Lower doses
may also be given to some elderly patients.
Children
The dose for babies and children is based on their weight. The
usual dose for newborn babies is 50mg per kg body weight per
day and for infants (1 to 4 weeks old) is 75mg per kg body weight
per day. The usual dose for children is 100mg per kg body weight
per day although higher doses of up to 4,000mg per day may be
given.
The daily dose may be divided into between two and six separate • reduction in blood cell count and anaemias which might 6. FURTHER INFORMATION
injections. Higher doses for severe infections are usually given by make you feel tired or dizzy The active substance in Benzylpenicillin Injection is benzylpenicillin
slow intravenous infusion (drip). • low levels of potassium in the blood sodium.
Meningitis: • high levels of sodium in the blood
• inflammation of the kidney What Benzylpenicillin Injection looks like and the contents of
The usual dose is 180-300mg per kg per day (up to 12g per day) the pack
for children up to 12 years old, 150mg per kg per day for infants • skin irritation, fever, headache, sore throat, sore muscles and
fast heartbeat particularly in patients being treated for syphilis Benzylpenicillin Injection is a white, crystalline powder, supplied in
(1 to 4 weeks old) and 100mg per kg per day for newborn babies. two strengths (600mg and 1,200mg) as a lyophilised plug in a
(a sexually transmitted disease)
Premature babies and neonates • diarrhoea, which may, rarely, have blood in it rubber stoppered glass vial. The 600mg vial is available in packs of
Lower doses may also be given to these groups. 2 (GP pack) and 25. The 1,200mg vial is available in packs of 25.
• thrush or infections with other germs
If you take more Benzylpenicillin Injection than you should • fits (convulsions).
POM
Irritation of the brain and shaking fits (convulsion) have been seen Reporting of side effects
in patients when very high doses of Benzylpenicillin Injection have
If you get any side effects, talk to your doctor, pharmacist or nurse. PL 06831/0213 Benzylpenicillin Injection 600mg
been given by mistake, in particular to patients with poor kidney
This includes any possible side effects not listed in this leaflet. You PL 06831/0284 Benzylpenicillin Injection 1200mg
function. can also report side effects directly via the Yellow Card Scheme at:
Marketing Authorisation Holder and Manufacturer
www.mhra.gov.uk/yellowcard.
4. POSSIBLE SIDE-EFFECTS Marketing Authorisation Holder:
By reporting side effects you can help provide more information on
Like all medicines, Benzylpenicillin Injection can cause side- Genus Pharmaceuticals, Linthwaite, Huddersfield, HD7 5QH, UK.
the safety of this medicine.
effects, although not everybody gets them. Manufacturers:
Tell your doctor immediately if you get any of the following side- 5. HOW TO STORE BENZYLPENICILLIN INJECTION Sandoz GmbH, A-6250 Kundl, Tirol, Austria.
effects:
Keep out of the sight and reach of children. Genus Pharmaceuticals, Linthwaite, Huddersfield, HD7 5QH, UK.
• skin rash or itchy skin
Benzylpenicillin Injection vials should be stored below 25°C. Once This leaflet was last revised in December 2018
• difficulty in breathing or tightness of the chest
• puffiness of the eyelids, face or lips the content of the vial has been mixed with an injection solution, it
should be used immediately.
• swelling or redness of the tongue
They should not use a bottle after the expiry date printed on the
• fever
bottle label. The expiry date refers to the last day of that month.
• joint pains
• swollen lymph nodes. Medicines should not be disposed of via wastewater or household
waste. Ask your pharmacist how to dispose of medicines no longer
The following side-effects have also been reported after either required. These measures will help protect the environment. 92797761805
long-term use or with high doses of your medicine:
*Trademark

GEN/BZP/PIL/336_05
14/09/2016